Central nervous system-derived extracellular vesicles: the next generation of neural circulating biomarkers?

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: June 19, 2024

Abstract The central nervous system (CNS) is integrated by glial and neuronal cells, both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos, which are protected during systemic circulation EVs. Having a window into molecular level processes happening open new avenue research. This raises particular point interest: can CNS-derived blood serve circulating biomarkers reflect pathological status neurological diseases? L1 cell adhesion molecule (L1CAM) widely reported biomarker identify peripheral blood. However, it has been demonstrated L1CAM also expressed outside CNS. Given principal data related neurodegenerative diseases, such multiple sclerosis, amyotrophic lateral Parkinson’s disease Alzheimer’s were obtained using L1CAM-positive EVs, efforts overcome present challenges its specificity required. In this sense, other surface glutamate aspartate transporter (GLAST) myelin oligodendrocyte glycoprotein (MOG), among others, have started used. Establishing panel EV analyse increase sensitivity necessary these types studies. review covers main evidence cerebrospinal fluid samples patients with focusing on technical possibilities their isolation. emerging mirror brain physiopathology, reflecting localized changes. Therefore, when hindrances research clinical applications overcome, novel disease-specific panels would discovered facilitate transformation from traditional medicine personalized medicine.

Language: Английский

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Extracellular vesicles transport RNA between cells: Unraveling their dual role in diagnostics and therapeutics

Molecular Aspects of Medicine, Journal Year: 2024, Volume and Issue: 99, P. 101302 - 101302

Published: Aug. 1, 2024

Modern methods of molecular diagnostics and therapy have revolutionized the field medicine in recent years by providing more precise effective tools for detecting treating diseases. This progress includes a growing exploration body's secreted vesicles, known as extracellular vesicles (EVs), both diagnostic therapeutic purposes. EVs are heterogeneous population lipid bilayer almost every cell type studied so far. They detected body fluids conditioned culture media from living cells. play crucial role communication between cells organs, locally over long distances. recognized their ability to transport endogenous RNA proteins cells, including messenger (mRNA), microRNA (miRNA), misfolded neurodegenerative proteins, several other biomolecules. review explores dual utilization EVs, serving not only purposes but also platform delivering molecules tissues. Through an composition, biogenesis, selective cargo packaging, we elucidate intricate mechanisms behind via highlighting potential use applications. Finally, it addresses challenges outlines prospective directions clinical EVs.

Language: Английский

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Prostate cancer and liquid biopsies: Clinical applications and challenges

International Journal of Urology, Journal Year: 2024, Volume and Issue: 31(6), P. 617 - 626

Published: March 29, 2024

Abstract Liquid biopsy has emerged as a valuable and minimally invasive tool for real‐time detection of clinically actionable abnormalities across various cancer types. Its applicability is particularly compelling in the realm prostate cancer, where novel therapeutic agents, including those targeting DNA repair systems, are under development. Despite these advancements, challenges persist effectively screening enhancing risk stratification, determining optimal approaches treating advanced disease. Consequently, there pressing need improved biomarkers to aid clinicians decision‐making within contexts. Cell‐free extracellular vesicle analysis have demonstrated promise diagnosis, prognostication, assessment treatment responses, identification emerging mechanisms resistance. Nevertheless, obstacles must be addressed before liquid biopsies can integrated into routine clinical practice. These encompass preanalytical considerations such sample collection storage, methods isolation enrichment, enhanced interpretation generated sequencing data. This review provides comprehensive overview current opportunities managing through blood‐based biopsy, highlighting progress made, acknowledging that remain. Additionally, we discuss next steps required effective implementation guiding personalized strategies cancer.

Language: Английский

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Standardized Reporting of Research on Exosomes to Ensure Rigor and Reproducibility

Advances in Wound Care, Journal Year: 2024, Volume and Issue: 13(11), P. 584 - 599

Published: June 18, 2024

Significance: The study of extracellular vesicles (EV), especially exosomes, has unlocked new avenues in understanding cellular communication and potential therapeutic avenues. Recent Advances: Advancements EV research have shown significant contributions from the International Society for Extracellular Vesicles (ISEV), establishing methodological standards. evolution MISEV guidelines 2014 to 2023 reflects enhanced rigor reproducibility. launch EV-TRACK platform promotes uniformity reproducibility by providing a centralized repository data sharing standardization practices. Furthermore, databases like EVpedia ExoCarta facilitated collaboration within scientific community. Concurrently, exosome-based therapies emerged as forefront area regenerative medicine targeted drug delivery, showcasing exosomes promoting tissue regeneration. Critical Issues: Despite advancements, field grapples with challenges such vesicular heterogeneity, isolation complexity, standardization. These issues impact clinical applications. inconsistency exosomal preparations trials poses efficacy safety. Future Directions: review outlines critical areas future research, including need technological innovation characterization, establishment standardized protocols, deeper exosome biology. also highlights reassess guidelines, develop characterization technologies, establish protocols overcome current limitations. Emphasis is placed on interdisciplinary address complexities biology, improve trial design, ultimately realize exosome's diagnostic potential. Continued evaluation rigorous validation are essential successful integration.

Language: Английский

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Extracellular Vesicles Linking Inflammation, Cancer and Thrombotic Risks

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: March 17, 2022

Extracellular vesicles (EVs) being defined as lipid-bilayer encircled particles are released by almost all known mammalian cell types and represent a heterogenous set of fragments that found in the blood circulation other body fluids. The current nomenclature distinguishes mainly three forms: microvesicles, which formed budding from plasma membrane; exosomes, released, when endosomes with intraluminal fuse apoptotic bodies representing cells. Their importance for great variety biological processes became increasingly evident last decade it was discovered they contribute to intercellular communication transferring nucleotides proteins recipient In this review, we delineate several aspects their isolation, purification, analysis; discuss some pitfalls have be considered therein. Further on, describe various cellular sources EVs explain different examples, how link cancer inflammatory conditions thrombotic processes. particular, elaborate on roles cancer-associated thrombosis COVID-19, two important paradigms, where local pathological systemic effects whole organism at least part via EVs. Finally, also possible developments field future might used biomarkers diagnosis, vehicles therapeutics.

Language: Английский

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Circulating microvesicles and exosomes in small cell lung cancer by quantitative proteomics

Clinical Proteomics, Journal Year: 2022, Volume and Issue: 19(1)

Published: Jan. 7, 2022

Abstract Background Early detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling circulating microvesicles and exosomes can be a high-throughput platform for discovery novel molecular insights putative Hence, this study aimed to investigate proteome dynamics plasma-derived newly diagnosed SCLC patients improve early detection. Methods Plasma-derived from 24 healthy controls were isolated plasma by either high-speed- or ultracentrifugation. Proteins derived these quantified using label-free mass spectrometry statistical analysis was carried out aiming at identifying significantly altered expressions between controls. Furthermore, expressed proteins subjected functional enrichment identify biological pathways implicated pathogenesis. Results Based on fold change (FC) ≥ 2 ≤ 0.5 AUC 0.70 ( p < 0.05), we identified 10 common 16 17 unique exosomes, respectively. Among proteins, found dysregulation coagulation factor XIII A (Log FC = − 1.1, 0.0003, 0.82, 95% CI: 0.69–0.96) complement H-related 4 1.2, 0.0005, CI; 0.67–0.97) compared individuals. Our data may indicate tumor-suppressing role blood involvement activation Conclusions In comparing individuals, several differentially identified. This is the first showing encompass specific with potential diagnostic attributes SCLC, thereby opening new opportunities non-invasive

Language: Английский

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Initial and ongoing tobacco smoking elicits vascular damage and distinct inflammatory response linked to neurodegeneration

Brain Behavior & Immunity - Health, Journal Year: 2023, Volume and Issue: 28, P. 100597 - 100597

Published: Jan. 29, 2023

Tobacco smoking is strongly linked to vascular damage contributing the development of hypertension, atherosclerosis, as well increasing risk for neurodegeneration. Still, involvement innate immune system in upon chronic tobacco use before onset clinical symptoms not fully characterized. Our data provide evidence that a single acute exposure elicits secretion extracellular vesicles expressing CD105 and CD49e from endothelial cells, granting further recognition early preclinical biomarkers damage. Furthermore, we investigated effects on healthy asymptomatic smokers compared never-smokers, focusing system. reveal distinct landscape representative stages clinically smokers, related diseases develop. These results indicate dysregulated immuno-vascular axis are otherwise considered individuals. The alterations characterized by increased CD36 expression blood monocyte subsets, neutrophilia plasma IL-18 reduced levels IL-33, IL-10 IL-8. Additionally, circulating BDNF elevated sTREM2, which associated with neurodegeneration, suggest considerable impact CNS function findings profound insight into initial ongoing potential neurodegenerative disorders, specifically cerebrovascular dysfunction dementia.

Language: Английский

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Size-Exclusion Chromatography Combined with Ultrafiltration Efficiently Isolates Extracellular Vesicles from Human Blood Samples in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3663 - 3663

Published: Feb. 11, 2023

There is still a need for an efficient method the isolation of extracellular vesicles (EVs) from human blood that provides reliable yield with acceptable purity. Blood source circulating EVs, but soluble proteins and lipoproteins hamper their concentration, isolation, detection. This study aims to investigate efficiency EV characterization methods not defined as "gold standard". EVs were isolated platelet-free plasma (PFP) patients healthy donors through size-exclusion chromatography (SEC) combined ultrafiltration (UF). Then, characterized using transmission electron microscopy (TEM), imaging flow cytometry (IFC), nanoparticle tracking analysis (NTA). TEM images showed intact roundish nanoparticles in pure samples. IFC detected prevalence CD63+ compared CD9+, CD81+, CD11c+ EVs. NTA confirmed presence small concentration ~1010 EVs/mL comparable when stratifying subjects by baseline demographics; conversely, differed according health status across affected autoimmune diseases (130 total, 65 idiopathic inflammatory myopathy (IIM) patients). Altogether, our data show method, i.e., SEC followed UF, approach isolate significant complex fluids, which might characterize disease conditions early.

Language: Английский

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Extracellular Vesicles of COVID-19 Patients Reflect Inflammation, Thrombogenicity, and Disease Severity

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5918 - 5918

Published: March 21, 2023

Severe COVID-19 infections present with cytokine storms, hypercoagulation, and acute respiratory distress syndrome, extracellular vesicles (EVs) being involved in coagulation inflammation. This study aimed to determine whether profiles EVs reflect disease severity. Thirty-six patients symptomatic infection mild/moderate/severe (12 each group) were analyzed. Sixteen healthy individuals served as controls. Coagulation EV characteristics tested by nanoparticle tracking analysis (NTA), flow cytometry, Western blot. While factors VII, V, VIII, vWF comparable, significant differences found patients' D-Dimer/fibrinogen/free protein S levels compared displayed higher percentages of small (<150 nm) increased expression exosome marker CD63. high platelet markers (CD41) (tissue factor activity, endothelial C receptor). moderate/severe expressed significantly immune cell (CD4/CD8/CD14) contained IL-6. We demonstrated that EVs, but not the profile, may serve biomarkers for elevated immune- vascular-related disease, play a role pathogenesis.

Language: Английский

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Extracellular vesicles from human plasma for biomarkers discovery: Impact of anticoagulants and isolation techniques

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(5), P. e0285440 - e0285440

Published: May 10, 2023

Extracellular vesicles (EVs) isolated from plasma are increasingly recognized as promising circulating biomarkers for disease discovery and progression, well therapeutic drug delivery. The scientific community underlined the necessity of standard operative procedures isolation storage EVs to ensure robust results. understanding impact pre-analytical variables is still limited some considerations about anticoagulants methods necessary. Therefore, we performed a comparison study between by ultracentrifugation affinity substrate separation EDTA sodium citrate. were characterized Nano Tracking Analysis, Western Blot, cytofluorimetric analysis surface markers, lipidomic analysis. While did not significantly alter any analyzed parameters, influenced size, purity, markers expression profile. Compared ultracentrifugation, yielded bigger particles highly enriched in tetraspanins (CD9, CD63, CD81), fatty acids glycerolipids, with predominant LDL- vLDL-like contamination. Herein, highlighted that method should be carefully evaluated prior design need standardized application discovery.

Language: Английский

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